On March 10, 2021 EMMAC Life Sciences Group, Europe’s largest independent cannabis company, reported that it is has signed a definitive agreement to be acquired by Curaleaf Holdings, Inc. (CSE: CURA) (OTCQX: CURLF) ("Curaleaf" or the "Company"), a leading U.S. provider of consumer products in cannabis, for a base consideration of approximately US$285 million to be paid in 85%/15% Curalfeaf shares and cash (Press release, EMMAC Life Sciences, MAR 10, 2021, View Source [SID1234576609]). Contingent consideration of up to $57 million will be paid in Curaleaf shares and cash in the same ratio based upon the successful achievement of performance milestones. The proposed transaction provides Curaleaf with a developed platform for entry into the European cannabis market.

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As Europe’s largest vertically integrated independent cannabis company, EMMAC’s platform brings cultivation, EU-GMP processing, distribution, and R&D operations across several key European medical cannabis markets, including the United Kingdom, Germany, Italy, Spain and Portugal. EMMAC also has an operational presence and partnerships in European Union countries that are enacting new medical cannabis access programs. EMMAC’s Portugal based cultivation facility is an industry leader in cannabis flower production cost.

Boris Jordan, Curaleaf Executive Chairman, stated, "Curaleaf’s acquisition of EMMAC, announced today, provides an advanced base to reach scale within the nascent European cannabis market and transform Curaleaf into a truly international cannabis consumer packaged goods company. The consumer and political liberalization trends around cannabis that are sweeping the U.S. are also increasingly taking hold in Europe. Curaleaf will seek to leverage our branded cannabis consumer packaged goods strategy across Europe, a market which provides for cross-border cannabis distribution. The European cannabis market has the potential to exceed the U.S. cannabis market over the long-term and will help fuel our growth for years to come."

Antonio Costanzo, Chief Executive Officer of EMMAC, said, "Curaleaf’s acquisition of EMMAC is not only a significant milestone for EMMAC, but for the European cannabis market as a whole. As part of Curaleaf, a well-capitalized leader of the U.S. cannabis market, EMMAC is poised to exploit the rapid pace of growth of the European market, driven by regulatory change and the increasing demand for access to premium quality cannabis products. The combination of Curaleaf and EMMAC creates a global platform to address these large new opportunities across Europe. With EMMAC’s science-led approach, wealth of local market experience, as well as our network of supply and distribution partnerships throughout Europe, we are now uniquely positioned to reinforce our place as one of Europe’s leaders in the production and supply of medical cannabis, wellness CBD, hemp and other derivative products."

Transaction Terms & Approvals

Curaleaf will acquire EMMAC for base consideration of £0.50 per share, comprised of approximately GBP£35 million in cash, approximately 16.774 million subordinate voting shares of Curaleaf (based on the exchange ratio of Curaleaf share for each EMMAC share agreed by the parties). At yesterday’s Curaleaf closing share price on the CSE, the base consideration is valued at $285 million2. An additional US$57 million3 consideration will be paid subject to performance-based earn-outs. Post-transaction, the former shareholders of EMMAC will have approximately 3% pro forma ownership of Curaleaf on a fully-diluted basis, before factoring in the performance-based earn-outs. The Curaleaf share consideration will be subject to a statutory four-month hold period as well as a lock-up agreement with each recipient restricting trading of the share received, with release of 5% from such restrictions at the end of each calendar quarter following the closing. The proposed transaction is expected to close early in the second quarter of 2021, subject to customary closing conditions and regulatory approval. The transaction has been unanimously approved by the boards of directors of both EMMAC and Curaleaf, with Mr. Boris Jordan abstaining from the voting.

Transaction Advisors

Stikeman Elliott LLP and Memery Crystal LLP acted as legal advisors to Curaleaf. Eight Capital acted as financial advisors and provided a fairness opinion to the Special Committee. Canaccord Genuity Group acted as financial advisor and provided a fairness opinion to EMMAC, and Norton Rose Fulbright acted as legal advisor to EMMAC. EMMAC’s European legal team was led by Hill Dickinson LLP in the United Kingdom.

On March 10, 2021 Transgene (Paris:TNG) (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, reported the expansion of a randomized, controlled study with TG4001 in combination with avelumab versus avelumab monotherapy in patients with HPV16-positive anogenital tumors (NCT: 03260023) (Press release, Transgene, MAR 10, 2021, View Source [SID1234621820]).

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Transgene has amended the initial Phase Ib/II trial protocol to enable a more rapid start of this important Phase II study based on encouraging Phase Ib/II trial data. This randomized Phase II trial will be supported by a continuing collaboration with the alliance of Merck KGaA, Darmstadt, Germany, and Pfizer, which is supplying avelumab. Transgene retains all rights to TG4001.

PHASE II TRIAL AIMS TO SHOW THE SUPERIORITY OF TG4001 + AVELUMAB OVER AVELUMAB MONOTHERAPY

The initial Phase Ib/II trial conducted in Europe (France and Spain) has been amended to include a randomized comparison of the combination of TG4001 with avelumab versus avelumab monotherapy in anogenital cancers. The submission of the amended protocol has been initiated in Europe. In addition, Transgene received US FDA clearance of the protocol under TG4001 IND. Patient enrollment is expected to start in Q2 2021.

The trial will focus on patients with recurrent or metastatic HPV16-positive anogenital cancer without liver metastases, including cervical, vulvar, vaginal, penile, and anal cancer. This population was shown in the Phase Ib/II study to derive improved clinical benefit from the combination regimen [1, 2].

Patients will be randomized to either receive the combination regimen of the therapeutic vaccine TG4001 and avelumab or avelumab alone.

The primary endpoint of the trial is progression-free survival (PFS) according to RECIST 1.1. Secondary endpoints include objective response rate (ORR), disease control rate (DCR), overall survival (OS) and a series of immunological parameters.

The Phase II trial will be supported by the extension of the collaboration with the alliance of Merck KGaA, Darmstadt, Germany, and Pfizer, which is supplying avelumab for this trial. Transgene retains all rights to TG4001.

An interim analysis will be performed after the enrollment of nearly 50 patients. Transgene expects to communicate the interim analysis data around the end of 2022. This timeline is based on patient enrollment starting in Q2 2021 and there being no major impact on recruitment from the Covid-19 pandemic.

Commenting on this novel investigational immunotherapy regimen, Prof. Christophe Le Tourneau, MD, Head of the Department of Drug Development and Innovation (D3i) at the Curie Institute and Principal Investigator of the trial, added: "I am very pleased that we are now moving ahead with a new part of this Phase II study. The promising data that we generated in the Phase Ib/II part of this study, in patients without liver metastases, gives me confidence that the amended study can generate the additional data needed to confirm the treatment benefits of the combination of TG4001 and avelumab in this patient population with very limited therapeutic options."

RECURRENT AND METASTATIC HPV16-POSITIVE ANOGENITAL CANCERS NEED BETTER TREATMENT OPTIONS

The Phase II trial focuses on indications where standard therapeutic options and immune checkpoint inhibitors have limited efficacy. These indications represent areas of important medical need; they include cervical, vulvar, vaginal, penile, and anal cancer. The trial will enroll patients who have received a maximum of one line of chemotherapy for the treatment of their recurrent or metastatic disease or who are not eligible for chemotherapy.

Transgene estimates the number of people diagnosed annually with these cancers to be around 25,000 patients per year (US, Europe 27, UK) [3-9]. In spite of recent progress, patients with these severe and heterogeneous malignancies need better treatment options, particularly after the recurrence of the disease: median overall survival is less than 11 months [10-13] and median progression-free survival is around 2 months [10-13].

Dr. Maud Brandely, MD, PhD, Chief Medical Officer of Transgene, concludes about this study: "I am pleased we have been able to use a methodologically sound trial design to move ahead with this randomized Phase II study quickly. The results from the initial Phase Ib/II study demonstrated the potential of the combination of TG4001 with an immune checkpoint inhibitor in this advanced disease setting. We observed encouraging clinical outcomes with a response rate reaching 34.8% and median progression-free survival of 5.6 months in patients without liver metastases. The observed median progression-free survival shows that this combination can induce a sustained and durable benefit, which may be based on the induction of a specific immune response. This study is expected to provide us with the data required to discuss the registration path of TG4001."

About the trial
The multi-center, open label, randomized Phase II trial (NCT03260023) is designed to compare the efficacy of the combination of TG4001 and avelumab versus avelumab alone in patients with advanced, recurrent and/or metastatic HPV16-positive anogenital cancers who have disease progression after a maximum of one line of systemic treatment, or who are not eligible for first-line chemotherapy.

Prof. Christophe Le Tourneau, M.D., PhD, Head of the Department of Drug Development and Innovation (D3i) at the Curie Institute, is the Principal Investigator of the study. The trial is being conducted in collaboration with Merck KGaA, Darmstadt, Germany, and Pfizer Inc. (NYSE: PFE), which are providing avelumab for the trial. Avelumab is co-developed and co-commercialized by Merck KGaA, Darmstadt, Germany and Pfizer Inc. Transgene will continue to be the sponsor of the trial and conduct the trial.

Patients will receive TG4001 at the dose of 5×107 pfu, SC, weekly for 6 weeks, every 2 weeks up to six months, and every 12 weeks thereafter, in combination with avelumab or avelumab alone at 800 mg, IV every two weeks, until disease progression. The primary endpoint of the trial is progression-free survival (PFS) according to RECIST 1.1. Secondary endpoints include objective response rate (ORR), disease control rate (DCR), overall survival (OS) and other immunological parameters. The trial could enroll up to 136 patients until the final analysis.

Patients with liver metastases will be followed in an ancillary arm and will be randomized to receive one of the treatment regimens; these patients will not be included in endpoint analyses.

About the data presented at SITC (Free SITC Whitepaper) 2020 and ESMO (Free ESMO Whitepaper) IO 2020 [1,2]
The results from the Phase Ib/II parts of the trial combining TG4001 with avelumab in HPV16-positive recurrent and/or metastatic malignancies were presented at SITC (Free SITC Whitepaper) 2020 [1] and ESMO (Free ESMO Whitepaper) IO 2020[2].

The combination of TG4001 and avelumab demonstrated anti-tumor activity (23.5% ORR) in patients with previously treated recurrent and/or metastatic HPV-related cancers (including patients with oropharyngeal cancers and anogenital cancers). Presence of liver metastases had a profound impact on the outcome in terms of ORR and PFS. In patients without liver metastases, an ORR of 34.8% and a median PFS of 5.6 months were achieved. The treatment induced HPV-specific T-cell responses and was associated with increased levels of immune cell infiltration in the tumors and expression of genes associated with activation of the immune system.

About TG4001
TG4001 is an investigational therapeutic vaccine based on a non-propagative, highly attenuated Vaccinia vector (MVA), which is engineered to express HPV16 antigens (E6 & E7) and an adjuvant (IL-2). TG4001 is designed to have a two-pronged antiviral approach: to alert the immune system specifically to cells presenting the HPV16 E6 and E7 antigens, that can be found in HPV16-related tumors, and to further stimulate the infection-clearing activity of the immune system through interleukin 2 (IL-2). TG4001 has been administered to more than 300 individuals, demonstrating good safety and promising efficacy results [1, 2, 14, 15]. Its mechanism of action and good safety profile make TG4001 an excellent candidate for combinations with other therapies in HPV-mediated solid tumors.

About HPV-Positive Cancers
HPV-positive cancers comprise a variety of malignancies, including anogenital cancers [3]. HPV-positive cancers include cervical [4], vaginal [5], vulvar [6], anal [7] and penile [8] cancers, i.e., approximately 25,000 cancers at metastatic stage eligible for a first-line treatment and in second line for a locoregional disease [9] (USA, EU 27, UK).

Current treatments mostly include chemoradiotherapy. However, better options are needed for advanced and metastatic HPV-positive cancers. It is thought that a therapeutic vaccine combined with other immunotherapeutic agents such as immune checkpoint inhibitors (ICIs) could provide a promising potential treatment option that would address this strong medical need [16,17]. With immune checkpoint inhibitors, median overall survival remains less than 11 months [10-13] and median progression-free survival is between 2 and 4 months [10-13].

On March 10, 2021 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases with significant unmet needs, reported that members of the management team will participate in a fireside chat at the Oppenheimer 31st Annual Healthcare Conference being held in a virtual setting on Wednesday, March 17, 2021 at 10:00am ET (Press release, Protara Therapeutics, MAR 10, 2021, View Source [SID1234576379]).

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A live audio webcast of the fireside chat can be accessed by visiting the Events and Presentations section of the Company’s website: View Source The webcast will be archived on the Company’s website for 90 days following the presentation.

On March 10, 2021 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, reported that the abstract, Voruciclib, a CDK9 inhibitor, downregulates MYC and inhibits proliferation of KRAS mutant cancers in preclinical models, was selected for an E-Poster Session presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 and will be available on April 10, 2021 (Press release, MEI Pharma, MAR 10, 2021, View Source [SID1234576396]). Voruciclib is an orally available inhibitor of cyclin-dependent kinase 9 (CDK9), part of a family of regulatory enzymes important to cell cycle regulation associated with cell proliferation and increased survival.

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KRAS mutated cancers are frequently associated with overexpression of MYC, a transcription factor regulating cell proliferation and growth. Inhibition of CDK9 leads to reduced transcription of MYC. As reported in the abstract to be presented at AACR (Free AACR Whitepaper) 2021, voruciclib decreased cell viability among multiple KRAS mutant cancer cell lines in vitro and was associated with significant tumor growth inhibition in vivo. Voruciclib treatment was associated with rapid inhibition of MYC phosphorylation at Ser62 resulting in a decrease in MYC protein. The research presented suggests that voruciclib could be an attractive therapeutic target for cancers driven by KRAS mutated cancers.

MEI pharma is also engaged in additional pre-clinical studies to explore the potential synergistic activity in various cancers of voruciclib in combination with drug-candidates that directly inhibit KRAS.

Details of MEI’s e-poster presentation at AACR (Free AACR Whitepaper) Annual Meeting 2021:

Abstract Title: Voruciclib, a CDK9 inhibitor, downregulates MYC and inhibits proliferation of KRAS mutant cancers in preclinical models
Poster Number: 1962
Poster Session Title: Cell Cycle
Date: Saturday, April 10, 2021

Abstracts and full session details can be found at View Source

About Voruciclib
Voruciclib is an orally administered cyclin-dependent kinase (CDK) inhibitor differentiated by its potent in vitro inhibition of CDK9 in addition to CDK6, 4 and 1. The CDK family of proteins are important cell cycle regulators.

CDK9 is a transcriptional regulator of the myeloid leukemia cell differentiation protein ("MCL1"), a member of the family of anti-apoptotic proteins which, when elevated, may prevent the cell from undergoing cell death. Inhibition of CDK9 blocks the production of MCL1, which is an established resistance mechanism to the B-cell lymphoma ("BCL2") inhibitor venetoclax (marketed as Venclexta).

CDK9 is also a transcriptional regulator of MYC proto-oncogene protein ("MYC"), a transcription factor regulating cell proliferation and growth which contributes to many human cancers and is frequently associated with poor prognosis and unfavorable patient survival. Targeting MYC directly has historically been difficult, but CDK9 is a transcriptional regulator of MYC and is a promising approach to target this oncogene.

Voruciclib is being currently evaluated in a Phase 1b trial evaluating dose and schedule in patients with acute myeloid leukemia ("AML") and B-cell malignancies.

On March 10, 2021 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage biotechnology company focused on discovering and developing novel small molecule drugs for the treatment of cancer and other life-threatening diseases, reported that the Company’s fourth quarter 2020 financial results will be released on Tuesday, March 16, 2021 (Press release, Calithera Biosciences, MAR 10, 2021, View Source [SID1234576412]). Company management will host a conference call on Tuesday, March 16, 2021 at 2:00 p.m. Pacific Time/ 5:00 p.m. Eastern Time to discuss the financial results and other recent corporate highlights.

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The press release and live audio webcast can be accessed via the Investor section of the Company’s website at www.calithera.com. The conference call can be accessed by dialing (855) 783-2599 (domestic) or (631) 485-4877 (international) and refer to conference ID 6250035. Please log in approximately 5-10 minutes before the event to ensure a timely connection. The archived webcast will remain available for replay on Calithera’s website for 30 days.